We thank Santilli et al for their interest in our article and for emphasizing the potential important contribution of psychological factors to the development of subclinical atherosclerosis. Psychological factors, such as depression, anger, sustained anxiety, and alexithymia, have been associated with increased carotid intima-media thickness in the Multi-Ethnic Study of Atherosclerosis (MESA) and in HIV-infected patients.1,2

There are many psychological, social, and cultural factors that may be potentially important determinants or modifiers of the atherosclerosis pathway from subclinical to overt vascular disease. Health-damaging psychological factors, such as stress, negative emotions, and health-promoting factors such as social support, are important predictors of cardiovascular disease (CVD) and stroke and may play a similar or larger role in CVD and stroke relative to traditional risk factors, including hypertension.3 However, available evidence addressing psychological, social, and cultural variables in relation to CVD and stroke and its intermediate phenotypes, such as carotid intima-media thickness and plaque in the general population as well as in diverse race-ethnic groups, is limited in the United States.

In the Northern Manhattan Study (NOMAS), prestroke social isolation was a predictor of poststroke outcomes,4 suggesting that a lack of social support contributes to poorer outcomes because of poor compliance, depression, and stress. Limited research has addressed sociocultural processes, such as culturally driven beliefs, attitudes, and behaviors, that may help explain vascular risk in the general population and in individuals at increased risk for CVD and stroke. In addition, little is known about vulnerability factors, such as ethnic-specific stressors or resiliency factors such as family cohesion and social support, that have been suggested as possible mechanisms that may exacerbate or buffer vascular risk among diverse age, sex, and race-ethnic groups. In addition, little is known about the association between neighborhood environments, either physical (eg, food and recreational access) or social (eg, social cohesion), and risk of atherosclerosis and CVD.5

The exact mechanism by which these psychosocial and cultural factors affect development of atherosclerosis is not well-understood. Alterations in the autonomic nervous system as a result of chronic health-damaging stressors may be the common mechanism linking them to cardiovascular responses and to an increased risk of atherosclerosis. More research is needed to elucidate the health-damaging and health-promoting biological mechanisms of psychological, social, and cultural factors on atherosclerosis.

Therefore, we agree with Santilli et al that psychological and sociocultural factors may have a major role in the development of subclinical and clinical CVD, and research in this area is critically needed for CVD health prevention and health promotion.